Nuclear molecular imaging technologies such as PET/CT and SPECT/CT are translational noninvasive methods because they offer sensitive means to assess metabolic-physiologic-molecular information of human diseases. Preclinical PET/CT and SPECT/CT are outstanding research platforms for further developing new imaging techniques that are directly translatable to clinical platforms of the same modalities. Currently, the pace of development cycles of clinical SPECT/CT systems is overshadowed by the rapid developmental efforts of clinical PET/CT. However, the development of preclinical SPECT/CT has made many advanced progresses over the past few years. The success of preclinical SPECT/CT's technical developments now propels the technical advances in clinical SPECT/CT systems. One example is multipinhole SPECT that became already standard in preclinical SPECT. In the clinical setting, although the multipinhole SPECT technology was developed even before the preclinical multipinhole SPECT and currently standard 'rotational' SPECT, the commercialization of clinical multipinhole SPECT was only recent. The most notable advantage of multipinhole SPECT, clinical or preclinical, is that it offers 'stationary' data acquisition for tomographic reconstruction. This stationary acquisition is similar to that possible through the ring detector system of coincidence PET, offering dynamic tomographic imaging capability that is not possible with rotational SPECT systems. UCSF Department of Radiology and Biomedical Imaging has invested significant resources in establishing the Center for Molecular and Functional Imaging (CMFI) that opened in 2003. Major research efforts at CMFI include translational nuclear molecular imaging research using SPECT/CT and PET/CT. The CMFI installed a medical cyclotron, built a state-of-the-art radiopharmaceutical laboratory, and integrated both preclinical and clinical molecular imaging facilities under one roof with animal vivarium that is under daily care by the University. The CMFI sited a state-of-the-art microPET/CT scanner in 2007. Through this High-End Instrumentation Grant mechanism, we are proposing to acquire multipinhole small animal SPECT combined with high-resolution in vivo CT, with dynamic imaging and high-sensitivity/high-throughput capabilities. This system is also capable of capturing small structural patterns of radiopharmaceuticals labeled with positron emitters resulting in high energy (511 keV) annihilation photons for signal detection, which is a great feature useful when finer spatial resolution scans, which are not possible with conventional coincidence PET, are desired. All of the fifteen projects identified in this grant application are highly translational research projects in oncology, neuroscience, and drug discovery and development. The translational research is the most advocated focus and mission of UCSF as well. In summary, we are confident that the new small animal SPECT/High-Energy/CT and the projects that will benefit from it will produce significant scientific outcomes that will help understand human disease and improve management.